Ribonucleotide reductase subunits M2 and p53R2 are potential biomarkers for metastasis of colon cancer
Ribonucleotide reductase subunits M2 and p53R2 are potential biomarkers for metastasis of colon cancer
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DOI：
10.3816/ccc.2007.n.007
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Yen, Yui
中科院分区：
文献类型：
--
作者：
Liu, Xiyong;Zhou, Bingsen;Yen, Yui
背景：核糖核苷二磷酸还原酶在将核糖核苷二磷酸转化为2‘-脱氧核糖核苷二磷酸的过程中起着关键作用，而2’-脱氧核糖核苷二磷酸是DNA修复和复制所必需的。为确定人核糖核苷酸还原酶小亚基M2(HRRM2)和p53依赖的人核糖核苷酸还原酶小亚基R2(P53R2)是否对癌细胞的侵袭能力起作用，采用基因转移技术构建了稳定的hRRM2和p53R2高表达载体。HRRM2的表达显著增强了KB和PC-3细胞的迁移能力，而p53R2过表达使KB和PC-3细胞的侵袭能力分别降低了50%和40%。此外，hRRM2增强了癌细胞诱导人脐静脉内皮细胞迁移的能力，但p53R2在转染体中降低了这种能力。患者和方法：为了进一步确定人类核糖核苷酸还原酶亚单位在癌症转移中的作用，使用了一个组织阵列，包括59个原发结肠腺癌和49个转移性结肠腺癌样本。采用免疫组织化学方法研究人核糖核苷酸还原酶亚基与肿瘤转移的关系。结果：单因素和多因素分析显示，p53R2与结肠腺癌的转移呈负相关(优势比0.23，P<0.05)，hRRM2增加结肠癌的转移风险，但无统计学意义。因此，hRRM2和p53R2在侵袭潜能中的相反调控可能在决定癌细胞的侵袭和转移表型中起关键作用。结论：核糖核苷酸还原酶小亚基的表达水平可作为预测未来人类肿瘤恶性潜能的生物标志物。
Background: Ribonucleoside diphosphate reductase plays a key role in converting ribonucleoside diphosphate to 2'-deoxyribonucleoside diphosphate, which is necessary for DNA repair and replication. To determine if human ribonucleotide reductase small subunit M2 (hRRM2) and p53-dependent human ribonucleotide reductase small subunit R2 (p53R2) play roles on invasion ability of cancer cells, the gene transferring technique was used to construct stable hRRM2 and p53R2 overexpression transfectants. Increase of hRRM2 dramatically enhanced the cell migration in KB and PC-3 cells, but p53R2 overexpression reduced cellular invasion potential to 50% and 40% in KB and PC-3 cells, respectively. Furthermore, hRRM2 enhanced cancer cells to induce the cell migration of Human Umbilical Vein Endothelial Cells, but p53R2 reduced this ability in transfectants. Patients and Methods: To further determine the role of human ribonucleotide reductase subunits on cancer metastasis, a tissue array, including 59 primary and 49 metastatic colon adenocarcinoma samples, was used. Immunohistochemistry was used to evaluate the relationship between human ribonucleotide reductase subunits and metastasis. Results: Univariate and multivariate analysis revealed that p53R2 is negatively related to the metastasis of colon adenocarcinoma samples (odds ratio, 0.23; P < 0.05); hRRM2 increases the risk of metastasis in colon cancer, but did not show significantly. Thus, opposing regulation of hRRM2 and p53R2 in invasion potential might play a critical role in determining the invasion and metastasis phenotype in cancer cells. Conclusion: The expression level of ribonucleotide reductase small subunits could serve as biomarkers to predict the malignancy potential of human cancers in the future.